Department of Medical Sciences, Jinhua College of Profession and Technology, and Department of Oncology, Jinhua People's Hospital, Jinhua 321007, PR China.
Mol Med Rep. 2012 Nov;6(5):1023-9. doi: 10.3892/mmr.2012.1043. Epub 2012 Aug 21.
The aim of this study was to investigate the effect of vascular endothelial growth factor-C (VEGF-C) expression in tumor-associated macrophages (TAMs) on lymphatic microvessel density (LMVD) and lymphatic endothelial cell proliferation (LECP) and to determine the role of VEGF-C expression in lymphangiogenesis in patients with breast cancer. Breast cancer tissue specimens confirmed by pathological analysis were obtained from 75 patients. Samples were observed by microscopy analysis after immunohistochemical double‑staining. The total number of TAMs and the number of VEGF-C-positive TAMs were determined. LMVD and LECP were calculated for the intratumoral and peritumoral areas. Correlation analysis was performed among these indexes, lymph vessel invasion (LVI) and lymph node metastasis in the peritumoral regions. Immunohistochemical double-staining demonstrated that VEGF-C was markedly expressed in TAMs. The number of TAMs, LMVD and LECP in the peritumoral areas was significantly higher than that in the intratumoral areas (P<0.001). We observed positive correlations between the following parameters: the number of TAMs and the peritumoral LMVD (P<0.001), the percentage of TAMs expressing VEGF-C and the peritumoral LMVD (P<0.001), the number of TAMs and the peritumoral LECP (P<0.001), and the percentage of TAMs expressing VEGF-C and the peritumoral LECP (P<0.001). Furthermore, the total number of TAMs and VEGF-C-positive TAMs, LMVD and LECP in cases with lymph node metastasis or LVI were significantly higher compared to those in cases without lymph node metastasis or LVI (P<0.01 or P<0.05). Our findings suggest that TAMs play a critical role in tumor-induced lymphangiogenesis through upregulating VEGF-C, which may contribute to lymphatic invasion in breast cancer.
本研究旨在探讨肿瘤相关巨噬细胞（TAMs）中血管内皮生长因子-C（VEGF-C）的表达对淋巴管密度（LMVD）和淋巴管内皮细胞增殖（LECP）的影响，并确定 VEGF-C 在乳腺癌淋巴管生成中的作用。通过病理分析从 75 例患者中获得了经证实的乳腺癌组织标本。使用免疫组织化学双重染色法观察显微镜分析后的样本。确定 TAMs 的总数和 VEGF-C 阳性 TAMs 的数量。计算肿瘤内和肿瘤周围区域的 LMVD 和 LECP。对这些指标、肿瘤周围区域的淋巴管侵犯（LVI）和淋巴结转移进行了相关性分析。免疫组织化学双重染色显示 VEGF-C 在 TAMs 中明显表达。肿瘤周围区域的 TAMs 数量、LMVD 和 LECP 明显高于肿瘤内区域（P<0.001）。我们观察到以下参数之间存在正相关：TAMs 数量与肿瘤周围 LMVD（P<0.001）、表达 VEGF-C 的 TAMs 百分比与肿瘤周围 LMVD（P<0.001）、TAMs 数量与肿瘤周围 LECP（P<0.001）和表达 VEGF-C 的 TAMs 百分比与肿瘤周围 LECP（P<0.001）。此外，淋巴结转移或 LVI 病例的 TAMs 总数和 VEGF-C 阳性 TAMs、LMVD 和 LECP 明显高于无淋巴结转移或 LVI 病例（P<0.01 或 P<0.05）。我们的研究结果表明，TAMs 通过上调 VEGF-C 在肿瘤诱导的淋巴管生成中发挥关键作用，这可能导致乳腺癌的淋巴侵袭。
